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1.
Prostate ; 84(4): 403-413, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38149792

RESUMEN

BACKGROUND: It is uncertain how long combination therapy should be continued in patients with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). We investigated the withdrawal effects of α1-adrenergic receptor blocker (AB) or 5α-reductase inhibitor (5ARI) following successful combination therapy. METHODS: This prospective, randomized, open-label, parallel trial enrolled 222 patients with BPH/LUTS who showed at least a seven-point improvement in International Prostate Symptom Score-total (IPSS-T) and a ≥ 20% reduction in prostate volume (PV) following the initiation of combination therapy. Patients were randomized in a 1:1:1 ratio into continued-combination, AB-withdrawal, and 5ARI-withdrawal groups. IPSS, overactive bladder symptom score, EuroQol-five-dimensional questionnaire (EQ-5D-5L), EuroQol-visual analog scale (EQ-VAS), prostate volume (PV), maximal flow rate, postvoid residual urine (PVR), and prostate-specific antigen level were assessed every 6 months for 24 months. The predictors of IPSS-T deterioration were evaluated. RESULTS: At Month 24, IPSS-T deterioration (≥2 point) was observed in 20/72 (27.8%) and 19/72 (26.4%) patients in the AB- and 5ARI-withdrawal groups, respectively. Among them, 4/72 (5.6%) and 4/70 (5.7%) patients required readdition of the withdrawn drug (p = 0.868). In the continued combination group, EQ-VAS improved at Month 24 compared to baseline (p = 0.028). At Month 24, the AB-withdrawal group showed improvements in EQ-5D-5L, EQ-VAS, and PVR (all p < 0.005), while the 5ARI-withdrawal group showed improvement in IPSS-S (p = 0.011). Diabetes mellitus was associated with IPSS-T deterioration at Month 24 (p = 0.020). CONCLUSIONS: In patients with BPH/LUTS who are reluctant to continue combination therapy, AB or 5ARI withdrawal may be offered in men with improvement in IPSS-T by at least seven points and reduction in PV by at least 20%.


Asunto(s)
Síntomas del Sistema Urinario Inferior , Hiperplasia Prostática , Retención Urinaria , Masculino , Humanos , Hiperplasia Prostática/tratamiento farmacológico , Estudios Prospectivos , Quimioterapia Combinada , Inhibidores de 5-alfa-Reductasa/uso terapéutico , Antagonistas Adrenérgicos alfa/uso terapéutico , Síntomas del Sistema Urinario Inferior/etiología , Retención Urinaria/etiología , Oxidorreductasas/uso terapéutico , Resultado del Tratamiento
2.
Int Neurourol J ; 27(2): 146-154, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37401026

RESUMEN

PURPOSE: Individual anatomical structural variations, including intravesical prostatic protrusion (IPP), prostatic urethral angle (PUA), prostatic urethral length, or prostatic apex shape, were correlated with micturition symptoms. We aimed to investigate the effects of these variables on micturition symptoms in men with benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS). METHODS: This observational study was based on data from 263 men with the first visit to health promotion center and without BPH/LUTS treatment between March 2020 and September 2022. A multivariate analysis was performed to determine the variables affecting total international prostate symptom score, maximum flow rate (Qmax), and voiding efficacy (postvoid residual volume to total bladder volume ratio). RESULTS: Of 263 patients, decreasing PUA increases the severity of international prostate symptoms score (mild, 141.9°; moderate, 136.0°; severe, 131.2°; P<0.015). A multivariate analysis reported that the total international prostate symptom score was correlated with age (P=0.002), PUA (P=0.007), and Qmax (P=0.008). Qmax was negatively associated with IPP (P=0.002). In subanalysis for large prostate volume (≥30 mL, n=81), international prostate symptom score was correlated with PUA (P=0.013), Qmax was correlated with prostatic apex shape (P=0.017), and length of proximal prostatic urethra (P=0.007). IPP was not identified as a significant factor. For small prostate volume (<30 mL, n=182), age (P=0.011) and prostate volume (P=0.004) are correlated with increasing Qmax. CONCLUSION: This study presented that individual anatomical structure variations influenced the micturition symptoms according to prostate volume. To identify the major resistant factors in men with BPH/LUTS, further studies are required to investigate which components played a role in major resistant factors for micturition symptoms.

3.
Medicina (Kaunas) ; 59(2)2023 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-36837469

RESUMEN

Background and Objectives: Non-contrast computed tomography (NCCT) is widely used to evaluate urolithiasis. The NCCT attenuation, measured in Hounsfield units (HU), has been evaluated to predict stone characteristics. We propose a novel parameter, linear calculus density (LCD), and analyze variables from NCCT imaging to predict calcium oxalate (CaOx) stones, which are common and challenging to fragment. Materials and Methods: We retrospectively reviewed the medical records of patients with urolithiasis between 2014 and 2017. Among those, 790 patients were included. Based on the NCCT pre-treatment, the maximal stone length (MSL), mean stone density (MSD), and stone heterogeneity index (SHI) were obtained. In addition, the variation coefficient of stone density (VCSD = SHI/MSD × 100) and linear calculus density (LCD = VCSD/MSL) were calculated. In accordance with the stone analysis, the patients were divided into two groups (CaOx and non-CaOx groups). The logistic regression model and receiver operating characteristic (ROC) curve were used for predictive modeling. Results: In the CaOx group, the SHI, VCSD, and LCD were more significant than in the non-CaOx group (all p < 0.001). SHI (OR 1.002, 95% CI 1.001-1.004, p < 0.001), VCSD (OR 1.028, 95% CI 1.016-1.041, p < 0.001), and LCD (OR 1.352, 95% CI 1.270-1.444, p < 0.001) were significant independent factors for CaOx stones in the logistic regression models. The areas under the ROC curve for predicting CaOx stones were 0.586 for SHI, 0.66 for VCSD, and 0.739 for LCD, with a cut-point of 2.25. Conclusions: LCD can be a useful new parameter to provide additional information to help discriminate CaOx stones before treatment.


Asunto(s)
Cálculos , Urolitiasis , Humanos , Oxalato de Calcio , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos
4.
Sci Rep ; 12(1): 20027, 2022 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-36414668

RESUMEN

Immunotherapy has a number of advantages over traditional anti-tumor therapy but can cause severe adverse reactions due to an overactive immune system. In contrast, a novel metabolic treatment approach can induce metabolic vulnerability through multiple cancer cell targets. Here, we show a therapeutic effect by inducing nucleotide imbalance and apoptosis in triple negative breast cancer cells (TNBC), by treating with cytosolic thymidylate 5'-phosphohydrolase (CT). We show that a sustained consumption of dTMP by CT could induce dNTP imbalance, leading to apoptosis as tricarboxylic acid cycle intermediates were depleted to mitigate this imbalance. These cytotoxic effects appeared to be different, depending on substrate specificity of the 5' nucleotide or metabolic dependency of the cancer cell lines. Using representative TNBC cell lines, we reveal how the TNBC cells were affected by CT-transfection through extracellular acidification rate (ECAR)/oxygen consumption rate (OCR) analysis and differential transcription/expression levels. We suggest a novel approach for treating refractory TNBC by an mRNA drug that can exploit metabolic dependencies to exacerbate cell metabolic vulnerability.


Asunto(s)
Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/patología , Timidina Monofosfato , Línea Celular Tumoral , Apoptosis , Monoéster Fosfórico Hidrolasas
5.
Sci Rep ; 11(1): 17092, 2021 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-34429450

RESUMEN

Permeation properties of hydrogen gas (H2) into nitrile butadiene rubber (NBR), ethylene propylene diene monomer (EPDM), and fluoroelastomer (FKM) which are the strong candidates for sealing material in H2 energy infrastructures, was quantified using a thermal desorption analysis gas chromatography (TDA GC) and a self-developed diffusion-analysis program. The samples were charged with H2 in a high-pressure chamber for 24 h then decompressed into atmosphere, and the mass of H2 released from the sample was measured as a function of elapsed time after decompression. The developed program calculated the total charging amount C0 and diffusivity D, which were then used to calculate the H2 solubility S and permeability P for variation of pressure. The samples were polymerized with and without carbon black (CB) filler in cylindrical shapes with different diameters. There was no appreciable pressure up to 12 MPa or diameter dependence investigated in this study on D, S and P. NBR and EPDM showed dual hydrogen diffusion with fast and slow diffusion behaviors caused by CB, whereas FKM showed a single diffusion behavior. The determined D are Dfast, NBR = (1.55 ± 0.28) × 10-10 m2/s, Dslow, NBR = (3.1 ± 0.5) × 10-11 m2/s, Dfast, EPDM = (3.65 ± 0.66) × 10-10 m2/s, Dslow, EPDM = (3.3 ± 0.5) × 10-11 m2/s, DFKM = (7.7 ± 0.8) × 10-11 m2/s. It appeared that the filler contributes to increase S and decrease D. The uncertainty analysis against the evaluated data was carried out, too, in order that the method could be applicable as a standard test for the permeation properties of various polymer membranes.

6.
Cancer Lett ; 504: 23-36, 2021 04 28.
Artículo en Inglés | MEDLINE | ID: mdl-33556544

RESUMEN

Despite technological advances in cancer treatment, the survival rate of patients with head and neck cancer (HNC) has not improved significantly. Many studies have shown that endoplasmic reticulum (ER) stress-related signals are associated with mitochondrial damage and that these signals determine whether cells maintain homeostasis or activate cell death programs. The unfolded protein response (UPR) is regulated by ER membrane proteins such as double-stranded RNA-activated protein kinase R(PKR)-like ER kinase (PERK), which directly activate transcription of chaperones or genes that function in redox homeostasis, protein secretion, or cell death programs. In this study, we focused on the role of mitophagy and ER stress-mediated cell death induced by DIM-C-pPhtBu in HNC cancer. We found that DIM-C-pPhtBu, a compound that activates ER stress in many cancers, induced lysosomal dysfunction, excessive mitophagy, and cell death in HNC cells. Moreover, DIM-C-pPhtBu strongly inhibited HNC progression in a xenograft model by altering mitophagy related protein expression. Taken together, the results demonstrate that DIM-C-pPhtBu induces excessive mitophagy and eventually UPR-mediated cell death in HNC cells, suggesting that new anti-cancer drugs could be developed based on the connection between mitophagy and cancer cell death.


Asunto(s)
Muerte Celular , Lisosomas/metabolismo , Mitofagia , Respuesta de Proteína Desplegada , Animales , Línea Celular Tumoral , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Reacción en Cadena de la Polimerasa , Especies Reactivas de Oxígeno/metabolismo
7.
Autophagy ; 17(4): 961-979, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-32164484

RESUMEN

AKT/PKB is downregulated by the ubiquitin-proteasome system (UPS), which plays a key role in cell survival and tumor progression in various types of cancer. The objective of this study was to determine the relationship between the sequential ubiquitination of lysine residues K284 to K214 in AKT and R-HSPA5 (the arginylated form of HSPA5), which contribute to the autophagic/lysosomal degradation of AKT when impaired proteasomal activity induces cellular stress. Results show that proteasome inhibitors (PIs) increased ATE1 (arginyltransferase 1)-mediated R-HSPA5 levels in a reactive oxygen species (ROS)-dependent manner. Further, binding of fully ubiquitinated AKT with R-HSPA5 induced AKT degradation via the autophagy-lysosome pathway. Specifically, the K48 (Lys48)-linked ubiquitinated form of AKT was selectively degraded in the lysosome with R-HSPA5. The deubiquitinase, USP7 (ubiquitin specific peptidase 7), prevented AKT degradation by inhibiting AKT ubiquitination via interaction with AKT. MUL1 (mitochondrial ubiquitin ligase activator of NFKB 1) also played a vital role in the lysosomal degradation of AKT by sequentially ubiquitinating AKT residues K284 to K214 for R-HSPA5-mediated autophagy. Consistent with this finding, despite HSPA5 arginylation, AKT was not degraded in mul1 KO cells. These results suggest that MUL1-mediated sequential ubiquitination of K284 to K214 may serve as a novel mechanism by which AKT is designated for lysosomal degradation. Moreover, binding of R-HSPA5 with fully ubiquitinated AKT is required for the autophagic/lysosomal degradation of AKT. Thus, modulating the MUL1-mediated non-proteasomal proteolysis mechanisms, such as sequential ubiquitination, may prove to be a novel therapeutic approach for cancer treatment.Abbreviations: AKT1: thymoma viral proto-oncogene 1; ATE1: arginyltransferase 1; ATG5: autophagy related 5; CASP3: caspase 3; EGFP: enhanced green fluorescent protein; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GSK3B; glycogen synthase kinase 3 beta; HA: hemagglutinin; HSPA5/GRP78/BIP: heat shock protein 5; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; MEF: mouse embryonic fibroblast; MUL1: mitochondrial ubiquitin ligase activator of NFKB1; NAC: N-acetylcysteine; NEK2: NIMA (never in mitosis gene a)-related expressed kinase 2; NH4Cl: ammonium chloride; PARP1: poly(ADP-ribose) polymerase family, member 1; PI: proteasome inhibitor; R-HSPA5: arginylated HSPA5; ROS: reactive oxygen species; SQSTM1: sequestome 1; Ub: ubiquitin; USP7: ubiquitin specific peptidase 7.


Asunto(s)
Arginina/metabolismo , Autofagia , Proteínas de Choque Térmico/metabolismo , Proteolisis , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ubiquitinación , Animales , Autofagosomas/efectos de los fármacos , Autofagosomas/metabolismo , Autofagia/efectos de los fármacos , Bortezomib/farmacología , Línea Celular Tumoral , Chaperón BiP del Retículo Endoplásmico , Humanos , Lisina/metabolismo , Lisosomas/efectos de los fármacos , Lisosomas/metabolismo , Ratones , Modelos Biológicos , Inhibidores de Proteasoma/farmacología , Proteolisis/efectos de los fármacos , Proto-Oncogenes Mas , Ubiquitina-Proteína Ligasas/metabolismo , Peptidasa Específica de Ubiquitina 7/metabolismo , Ubiquitinación/efectos de los fármacos
8.
Sensors (Basel) ; 20(22)2020 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-33198298

RESUMEN

A long-range wide area network (LoRaWAN) is one of the leading communication technologies for Internet of Things (IoT) applications. In order to fulfill the IoT-enabled application requirements, LoRaWAN employs an adaptive data rate (ADR) mechanism at both the end device (ED) and the network server (NS). NS-managed ADR aims to offer a reliable and battery-efficient resource to EDs by managing the spreading factor (SF) and transmit power (TP). However, such management is severely affected by the lack of agility in adapting to the variable channel conditions. Thus, several hours or even days may be required to converge at a level of stable and energy-efficient communication. Therefore, we propose two NS-managed ADRs, a Gaussian filter-based ADR (G-ADR) and an exponential moving average-based ADR (EMA-ADR). Both of the proposed schemes operate as a low-pass filter to resist rapid changes in the signal-to-noise ratio of received packets at the NS. The proposed methods aim to allocate the best SF and TP to both static and mobile EDs by seeking to reduce the convergence period in the confirmed mode of LoRaWAN. Based on the simulation results, we show that the G-ADR and EMA-ADR schemes reduce the convergence period in a static scenario by 16% and 68%, and in a mobility scenario by 17% and 81%, respectively, as compared to typical ADR. Moreover, we show that the proposed schemes are successful in reducing the energy consumption and enhancing the packet success ratio.

9.
Sensors (Basel) ; 20(9)2020 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-32384656

RESUMEN

A long-range wide area network (LoRaWAN) adapts the ALOHA network concept for channel access, resulting in packet collisions caused by intra- and inter-spreading factor (SF) interference. This leads to a high packet loss ratio. In LoRaWAN, each end device (ED) increments the SF after every two consecutive failed retransmissions, thus forcing the EDs to use a high SF. When numerous EDs switch to the highest SF, the network loses its advantage of orthogonality. Thus, the collision probability of the ED packets increases drastically. In this study, we propose two SF allocation schemes to enhance the packet success ratio by lowering the impact of interference. The first scheme, called the channel-adaptive SF recovery algorithm, increments or decrements the SF based on the retransmission of the ED packets, indicating the channel status in the network. The second approach allocates SF to EDs based on ED sensitivity during the initial deployment. These schemes are validated through extensive simulations by considering the channel interference in both confirmed and unconfirmed modes of LoRaWAN. Through simulation results, we show that the SFs have been adaptively applied to each ED, and the proposed schemes enhance the packet success delivery ratio as compared to the typical SF allocation schemes.

10.
Biosens Bioelectron ; 126: 381-388, 2019 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-30469076

RESUMEN

This research demonstrated the electrochemical modification of low-cost titanium (Ti) metal substrate with gold nanoparticles (AuNPs) for the aptamer-based detection of cardiac troponin I (cTnI). AuNPs were deposited onto Ti sheets by the potential-step deposition method with high density and homogeneity as well as good crystallinity. It was then applied as a transducer to immobilize a thiol-functionalized DNA aptamer via the self-assembled monolayer mechanism for the specific binding of cTnI. This was verified through electrochemical and morphological analyses. The aptasensor could detect cTnI in a linear range of 1-1100 pM with a detection limit of ca. 0.18 pM. The aptasensor showed high sensitivity and specificity to cTnI over other interfering compounds with good recoveries in the diluted human serum samples.


Asunto(s)
Técnicas Biosensibles , Técnicas Electroquímicas , Troponina I/aislamiento & purificación , Aptámeros de Nucleótidos/química , Oro/química , Grafito/química , Humanos , Límite de Detección , Nanopartículas del Metal/química , Troponina I/sangre , Troponina I/química
11.
Sci Rep ; 8(1): 12520, 2018 08 21.
Artículo en Inglés | MEDLINE | ID: mdl-30131570

RESUMEN

Although TRAIL can directly induce cell death in some cancer cells, it appears that TRAIL resistance exists in many cancers. This study focuses on anti-cancer drugs for TRAIL-resistant head and neck cancer (HNC) to provide further progress toward effective cancer therapy. Results indicate in TRAIL-resistant HNC cells, that combined TRAIL and VPA treatment greatly reduced cell viability and therefore induced cell death, relative to treatment with TRAIL or VPA alone. A caspase-dependent signaling pathway was demonstrated, and combined treatment with TRAIL and VPA also significantly decreased the expression of HDAC4. When we pretreated cells with z-VAD followed by combined treatment with TRAIL and VPA, cell death was blocked with no reduction in expression of HDAC4. To confirm that cell death involved HDAC4 in HNC cells, we knocked down expression of HDAC4 with siRNA, followed by treatment with TRAIL and VPA. Results showed that loss of HDAC4 sensitized the TRAIL-resistant HNC cells to apoptotic cell death. Finally, we showed elevated expression of HDAC4 in HNC tissues compared to normal tissues obtained from the same patients. In conclusion, we suggest that combined VPA and TRAIL treatment may be a promising therapy for HNC via HDAC4 degradation.


Asunto(s)
Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Histona Desacetilasas/química , Proteínas Represoras/química , Ligando Inductor de Apoptosis Relacionado con TNF/farmacología , Ácido Valproico/farmacología , Caspasas/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Sinergismo Farmacológico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/metabolismo , Histona Desacetilasas/genética , Humanos , Proteolisis , Proteínas Represoras/genética , Transducción de Señal/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos
12.
Sci Rep ; 8(1): 2277, 2018 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-29396442

RESUMEN

The accumulation and differentiation of adipocytes contribute to the development of obesity and metabolic diseases. It is well-known that interactions of transcription factors such as peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), and endoplasmic reticulum (ER) stress are required for adipogenesis. Recently, use of nonthermal atmospheric plasma (NTP) is expanding from the biomedical field into various other fields. In this study, we investigated whether nonthermal plasma-treated solution (NTS) has an inhibitory effect on adipogenesis and elucidated its mechanisms. Our results demonstrated that NTS significantly inhibited pre-adipocyte differentiation into adipocytes based on Oil Red O staining and triglyceride accumulation. Moreover, NTS treatment suppressed the mRNA and protein expression levels of key adipogenic transcription factors, and adipocyte-specific genes. NTS also down-regulated endoplasmic reticulum stress-related proteins. Consistent with in vitro studies, an animal study using a mouse model of diet-induced obesity showed that NTS treatment reduced body weight and fat, ER stress/UPR, triglyceride, and adipogenic marker level without altering food intake. These findings indicate that NTS inhibits adipogenic differentiation, and provide a mechanistic explanation of the inhibitory effect of NTS on adipogenesis. Taken together, our results suggest that NTS might be useful to treat obesity and obesity-related diseases.


Asunto(s)
Adipocitos/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Retículo Endoplásmico/efectos de los fármacos , Lipogénesis/efectos de los fármacos , Gases em Plasma , Soluciones/química , Estrés Fisiológico/efectos de los fármacos , Células 3T3-L1 , Adipocitos/fisiología , Animales , Peso Corporal , Modelos Animales de Enfermedad , Ratones , Obesidad/prevención & control , Soluciones/administración & dosificación
13.
Autophagy ; 14(3): 385-403, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29260979

RESUMEN

HSPA5/GRP78/BiP plays an important role in cell survival or tumor progression. For these reasons, HSPA5 is an emerging therapeutic target in cancer development. Here we report that HSPA5 contributes to head and neck cancer (HNC) survival via maintenance of lysosomal activity; however, a nonthermal plasma (NTP, considered as a next-generation cancer therapy)-treated solution (NTS) inhibits HNC progression through HSPA5-dependent alteration of lysosomal activity. HSPA5 prevents NTS-induced lysosome inhibition through lysosomal-related proteins or regulation of gene expression. However, NTS-induced MUL1/MULAN/GIDE/MAPL (mitochondrial ubiquitin ligase activator of NFKB 1) leads to downregulation of HSPA5 via K48-linked ubiquitination at the lysine 446 (K446) residue. MUL1 knockdown hinders NTS-induced lysosome inhibition or cytotoxicity through the reduction of HSPA5 ubiquitination in HNC cells. While MUL1 was suppressed, HSPA5 was overexpressed in tissues of HNC patients. NTS strongly inhibited HNC progression via alterations of expression of MUL1 and HSPA5, in vivo in a xenograft model. However, NTS did not induce inhibition of tumor progression or HSPA5 reduction in MUL1 knockout (KO) HNC cells which were generated by CRISPR/Cas9 system. The data provide compelling evidence to support the idea that the regulation of the MUL1-HSPA5 axis can be a novel strategy for the treatment of HNC.


Asunto(s)
Autofagia/fisiología , Neoplasias de Cabeza y Cuello/metabolismo , Proteínas de Choque Térmico/metabolismo , Lisosomas/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Línea Celular Tumoral , Supervivencia Celular/fisiología , Chaperón BiP del Retículo Endoplásmico , Humanos , Ratones , Ubiquitinación/fisiología , Ensayos Antitumor por Modelo de Xenoinjerto
14.
Gut Liver ; 12(2): 183-189, 2018 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-29212310

RESUMEN

BACKGROUND/AIMS: Knowledge regarding the quality metrics of fecal immunochemical test (FIT)-based colorectal cancer screening programs is limited. The aim of this study was to investigate the performance and quality metrics of a FIT-based screening program. METHODS: In our screening program, asymptomatic subjects aged ≥50 years underwent an annual FIT, and subjects with positive FIT results underwent a subsequent colonoscopy. The performance of the FIT and colonoscopy was analyzed in individuals with a positive FIT who completed the program between 2009 and 2015 at a university hospital. RESULTS: Among the 51,439 screened participants, 75.1% completed the FIT. The positive rate was 1.1%, and the colonoscopy completion rate in these patients was 68.6%. The positive predictive values of cancer and advanced neoplasia were 5.5% and 19.1%, respectively. The adenoma detection rate in the patients who underwent colonoscopy after a positive FIT was 48.2% (60.0% for men and 33.6% for women). The group with the highest tertile quantitative FIT level showed a significantly higher detection rate of advanced neoplasia than the group with the lowest tertile (odds ratio, 2.6; 95% confidence interval, 1.4 to 5.1; p<0.001). CONCLUSIONS: The quality metrics used in the United States and Europe may be directly introduced to other countries, including Korea. However, the optimal quality metrics should be established in each country.


Asunto(s)
Colonoscopía/métodos , Neoplasias Colorrectales , Detección Precoz del Cáncer , Mucosa Intestinal/patología , Anciano , Colonoscopía/estadística & datos numéricos , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/inmunología , Detección Precoz del Cáncer/métodos , Heces/química , Femenino , Humanos , Inmunoquímica/métodos , Masculino , Persona de Mediana Edad , Sangre Oculta , Valor Predictivo de las Pruebas , República de Corea/epidemiología
15.
Gut Liver ; 11(6): 821-827, 2017 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-28750489

RESUMEN

BACKGROUND/AIMS: The adoption of colonoscopy as a primary colorectal cancer (CRC) screening technique has been argued for in Korea, without evidence of patient preferences. This study aimed to investigate patients' preferences for the primary CRC screening test for the National Cancer Screening Program (NCSP). METHODS: Between June and August 2016, 414 individuals aged ≥50 years who participated in the NCSP were prospectively invited to complete a questionnaire regarding their preferences for the primary CRC screening test and the reasons for their selection. RESULTS: Among the 396 respondents who completed the questionnaire, 124 individuals (31.3%) preferred the fecal immunochemical test (FIT), whereas 272 individuals (68.7%) preferred colonoscopy. Elderly participants preferred the FIT (p<0.001), whereas participants with a higher education level (p=0.030), a higher income level (p=0.009), or individuals with a family member (p=0.028) or acquaintance (p=0.013) with a history of CRC preferred colonoscopy. Only 12.9% of participants had a bad experience with a previous FIT; however, 39.3% of participants had a bad experience with a previous colonoscopy. CONCLUSIONS: Colonoscopy was preferred to FIT in a 2.2:1 ratio as the primary CRC screening test for the NCSP. Patients' preference for colonoscopy should be considered for the NCSP in Korea.


Asunto(s)
Colonoscopía/psicología , Neoplasias Colorrectales/psicología , Detección Precoz del Cáncer/psicología , Tamizaje Masivo/psicología , Prioridad del Paciente , Anciano , Colonoscopía/métodos , Neoplasias Colorrectales/diagnóstico , Detección Precoz del Cáncer/métodos , Femenino , Humanos , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Sangre Oculta , República de Corea , Encuestas y Cuestionarios
16.
Oncotarget ; 8(66): 110474-110489, 2017 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-29299162

RESUMEN

AKT (also known as protein kinase B, PKB) plays an important role in cell survival or tumor progression. For these reasons, AKT is an emerging target for cancer therapeutics. Previously our studies showed that mitochondrial E3 ubiquitin protein ligase 1 (MUL1, also known as MULAN/GIDE/MAPL) is suppressed in head and neck cancer (HNC) and acts as negative regulator against AKT. However, the MUL1 regulatory mechanisms remain largely unknown. Here we report that cisplatin (CDDP) induces thyroid cancer cell death through MUL1-AKT axis. Specifically, CDDP-induced MUL1 leads to ubiquitylation of active form of AKT. We also observed that the role of forkhead box O3 (FOXO3) is pivotal in CDDP-induced MUL1 regulation. FOXO3 knock-downed cells show resistance against CDDP-mediated MUL1-AKT axis. CDDP-mediated intracellular ROS increment plays an important role in FOXO3-MUL1-AKT signal pathway. The data provide compelling evidence to support the idea that the regulation of FOXO3-MUL1-AKT axis can be a novel strategy for the treatment of HNC with CDDP.

17.
Artículo en Inglés | MEDLINE | ID: mdl-27638114

RESUMEN

Antimicrobial-resistant (AR) enterococci have emerged as leading nosocomial pathogens. Transmission of AR Enterococci from animals to humans has been demonstrated. However, there is limited information on the transmission of enterococci from horses to humans. To address this issue, we characterized 260 enterococci isolated from horse-associated samples in Korea in 2013 based on their AR profiles and virulence traits. AR profiling revealed an average ratio of AR enterococci of 23.8%. Seven isolates (2.7%) were multidrug-resistant Enterococcus faecalis. Most tetracycline-resistant enterococci harbored either tetM or tetL or both genes; genes conferring resistance to other antimicrobials were detected at low rates. Biofilm formation and gelatinase activity were observed in 51.1% and 47.7% of isolates, respectively; most were E. faecalis harboring the gelE gene. Evidence of transmission of AR enterococci between horses and their environments was provided by pulsed-field gel electrophoresis, and highlights the risk of AR enterococcus transmission to horse riders and handlers through close contact.


Asunto(s)
Farmacorresistencia Bacteriana Múltiple , Enterococcus/efectos de los fármacos , Enterococcus/patogenicidad , Caballos/microbiología , Animales , Proteínas Bacterianas/genética , Biopelículas , Infección Hospitalaria/microbiología , Infección Hospitalaria/transmisión , Farmacorresistencia Microbiana/genética , Farmacorresistencia Bacteriana Múltiple/genética , Electroforesis en Gel de Campo Pulsado , Enterococcus/enzimología , Enterococcus/genética , Enterococcus faecalis/genética , Heces/microbiología , Gelatinasas/biosíntesis , Infecciones por Bacterias Grampositivas/transmisión , Humanos , Pruebas de Sensibilidad Microbiana , República de Corea , Virulencia/genética
18.
Mycobiology ; 44(2): 112-6, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27433122

RESUMEN

We encountered an unfamiliar ascomycete fruiting body, fitting characteristics of the genus Kretzschmaria, which features in a stipitate ascigerous stroma with carbonaceous interior and disintegrating perithecia. In this study, we report and characterize a new species of the decaying fungus. Compared to other species, one of the notable features of this specimen (TPML150908-046) is its stromatal size (up to 15 cm). Although TPML150908-046 is morphologically similar to K. milleri and K. sandvicensis, it differs sharply from both species in apical ring size (TPML150908-046, 6.5~10.5 µm; K. milleri, 11~16 µm) and ascospore width (TPML150908-046, 10.5~17 µm; K. sandvicensis, 8.5~11.5 µm). Phylogenetic trees based on ß-tubulin, ITS, and RPB2 sequences showed that our collection clustered with K. sandvicensis, with the respective similarities for these sequences being 95.6%, 91.3%, and 97.7%, signifying it as another species. With these results, we report it as a new species, which we call Kretzschmaria quercicola sp. nov.

19.
J Med Entomol ; 53(3): 584-590, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-26957392

RESUMEN

A survey of reptile-associated ticks and their infection status with severe fever with thrombocytopenia syndrome (SFTS) virus was conducted to determine the relative abundance and distribution among lizards, skinks, and snakes in the Republic of Korea (ROK). In total, 132 reptiles, including 49 lizards (two species), 15 skinks (one species), and 68 snakes (eight species) were collected. In total, 84 ixodid ticks belonging to two genera (Ixodes and Amblyomma) were collected from 28/132 (21.2%) lizards, skinks, and snakes. Ixodes nipponensis Kitaoka & Saito was only collected from lizards and skinks, while Amblyomma testudinarium Koch was only collected from snakes. Takydromus wolteri had the highest tick index (0.7; total number ticks/total number collected hosts) among lizards and skinks, while Rhabdophis tigrinus had the highest tick index (2.2) among the snakes. Ixodes nipponensis larvae and nymphs accounted for 11.1% and 88.9%, respectively, of all ticks collected from lizards and skinks, while only A. testudinarium nymphs were collected from snakes. Nymphs of both species of ticks were collected from lizards and skinks from April to October, while I. nipponensis larvae were collected only from September to October. Ixodes nipponensis larvae and nymphs were preferentially attached to the lateral trunk (83.3%) and the foreleg axillae (16.7%) of lizards and skinks. SFTS virus was detected in both I. nipponensis and A. testudinarium collected from lizards and snakes. Phylogenetic analysis of SFTS viruses of ticks collected from two lizards and one snake demonstrated close relationships with SFTS virus strains observed from humans and ticks in the ROK, China, and Japan. These results implicate lizards and snakes as potential hosts of SFTS virus.


Asunto(s)
Infecciones por Bunyaviridae/veterinaria , Insectos Vectores/virología , Ixodes/virología , Ixodidae/virología , Lagartos/virología , Phlebovirus/aislamiento & purificación , Serpientes/virología , Animales , Infecciones por Bunyaviridae/transmisión , Infecciones por Bunyaviridae/virología , Insectos Vectores/fisiología , Ixodes/fisiología , Ixodidae/fisiología , Phlebovirus/clasificación , Phlebovirus/genética , Filogenia , República de Corea
20.
J Vet Sci ; 17(2): 199-206, 2016 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-26645344

RESUMEN

Limited information is available regarding horse-associated antimicrobial resistant (AR) Escherichia (E.) coli. This study was designed to evaluate the frequency and characterize the pattern of AR E. coli from healthy horse-associated samples. A total of 143 E. coli (4.6%) were isolated from 3,078 samples collected from three national racetracks and 14 private horse-riding courses in Korea. Thirty of the E. coli isolates (21%) showed antimicrobial resistance to at least one antimicrobial agent, and four of the AR E. coli (13.3%) were defined as multi-drug resistance. Most of the AR E. coli harbored AR genes corresponding to their antimicrobial resistance phenotypes. Four of the AR E. coli carried class 1 integrase gene (intI1), a gene associated with multi-drug resistance. Pulsed-field gel electrophoretic analysis showed no genetic relatedness among AR E. coli isolated from different facilities; however, cross-transmissions between horses or horses and environments were detected in two facilities. Although cross-transmission of AR E. coli in horses and their environments was generally low, our study suggests a risk of transmission of AR bacteria between horses and humans. Further studies are needed to evaluate the risk of possible transmission of horse-associated AR bacteria to human communities through horse riders and horse-care workers.


Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple , Infecciones por Escherichia coli/veterinaria , Enfermedades de los Caballos/epidemiología , Animales , Escherichia coli , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/microbiología , Heces/microbiología , Enfermedades de los Caballos/microbiología , Caballos , Filogenia , Prevalencia , República de Corea/epidemiología , Análisis de Secuencia de ADN/veterinaria
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